Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.

Helicobacter pylori are responsible for the induction of chronic gastric inflammation progressing to atrophy, metaplasia, and gastric cancer. The overexpression of Cathepsin X/Z (Ctsz) in H. pylori-infected mucosa and gastric cancer is mediated predominantly by an augmented migration of ctsz(-/-)pos...

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Autores principales: Sabine Krueger, Anja Bernhardt, Thomas Kalinski, Martin Baldensperger, Michael Zeh, Anne Teller, Daniela Adolf, Thomas Reinheckel, Albert Roessner, Doerthe Kuester
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:612aaf29cdcb401cb9bdc5d0d3f564a32021-11-18T09:01:59ZInduction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.1932-620310.1371/journal.pone.0070242https://doaj.org/article/612aaf29cdcb401cb9bdc5d0d3f564a32013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23936173/?tool=EBIhttps://doaj.org/toc/1932-6203Helicobacter pylori are responsible for the induction of chronic gastric inflammation progressing to atrophy, metaplasia, and gastric cancer. The overexpression of Cathepsin X/Z (Ctsz) in H. pylori-infected mucosa and gastric cancer is mediated predominantly by an augmented migration of ctsz(-/-)positive macrophages and the up-regulation of Ctsz in tumor epithelium. To explore the Ctsz-function in the context of chronic inflammation and the development of preneoplastic lesions, we used Ctsz-deficient mice in a H. pylori gastritis model. Ctsz (-/-) and wild-type (wt) mice were infected with H. pylori strain SS1. The mice were sacrificed at 24, 36, and 50 weeks post infection (wpi). The stomach was removed, and gastric strips were snap-frozen or embedded and stained with H&E. Tissue sections were scored for epithelial lesions and inflammation. Ki-67 and F4/80 immunostaining were used to measure epithelial cell proliferation and macrophage infiltration, respectively. The upregulation of compensating cathepsins and cytokines were confirmed by Western blotting and quantitative RT-PCR. SS1-infected wt and ctsz (-/-) mice showed strong inflammation, foveolar hyperplasia, atrophy, and cystically-dilated glands. However, at 50 wpi, ctsz (-/-) mice developed significantly more severe spasmolytic polypeptide-expressing metaplasia (SPEM), showed enhanced epithelial proliferation, and higher levels of infiltrating macrophages. Induction of cytokines was higher and significantly prolonged in ctsz (-/-) mice compared to wt. Ctsz deficiency supports H. pylori-dependent development of chronic gastritis up to metaplasia, indicating a protective, but not proteolytic, function of Ctsz in inflammatory gastric disease.Sabine KruegerAnja BernhardtThomas KalinskiMartin BaldenspergerMichael ZehAnne TellerDaniela AdolfThomas ReinheckelAlbert RoessnerDoerthe KuesterPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e70242 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Sabine Krueger
Anja Bernhardt
Thomas Kalinski
Martin Baldensperger
Michael Zeh
Anne Teller
Daniela Adolf
Thomas Reinheckel
Albert Roessner
Doerthe Kuester
Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.
description Helicobacter pylori are responsible for the induction of chronic gastric inflammation progressing to atrophy, metaplasia, and gastric cancer. The overexpression of Cathepsin X/Z (Ctsz) in H. pylori-infected mucosa and gastric cancer is mediated predominantly by an augmented migration of ctsz(-/-)positive macrophages and the up-regulation of Ctsz in tumor epithelium. To explore the Ctsz-function in the context of chronic inflammation and the development of preneoplastic lesions, we used Ctsz-deficient mice in a H. pylori gastritis model. Ctsz (-/-) and wild-type (wt) mice were infected with H. pylori strain SS1. The mice were sacrificed at 24, 36, and 50 weeks post infection (wpi). The stomach was removed, and gastric strips were snap-frozen or embedded and stained with H&E. Tissue sections were scored for epithelial lesions and inflammation. Ki-67 and F4/80 immunostaining were used to measure epithelial cell proliferation and macrophage infiltration, respectively. The upregulation of compensating cathepsins and cytokines were confirmed by Western blotting and quantitative RT-PCR. SS1-infected wt and ctsz (-/-) mice showed strong inflammation, foveolar hyperplasia, atrophy, and cystically-dilated glands. However, at 50 wpi, ctsz (-/-) mice developed significantly more severe spasmolytic polypeptide-expressing metaplasia (SPEM), showed enhanced epithelial proliferation, and higher levels of infiltrating macrophages. Induction of cytokines was higher and significantly prolonged in ctsz (-/-) mice compared to wt. Ctsz deficiency supports H. pylori-dependent development of chronic gastritis up to metaplasia, indicating a protective, but not proteolytic, function of Ctsz in inflammatory gastric disease.
format article
author Sabine Krueger
Anja Bernhardt
Thomas Kalinski
Martin Baldensperger
Michael Zeh
Anne Teller
Daniela Adolf
Thomas Reinheckel
Albert Roessner
Doerthe Kuester
author_facet Sabine Krueger
Anja Bernhardt
Thomas Kalinski
Martin Baldensperger
Michael Zeh
Anne Teller
Daniela Adolf
Thomas Reinheckel
Albert Roessner
Doerthe Kuester
author_sort Sabine Krueger
title Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.
title_short Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.
title_full Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.
title_fullStr Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.
title_full_unstemmed Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.
title_sort induction of premalignant host responses by cathepsin x/z-deficiency in helicobacter pylori-infected mice.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/612aaf29cdcb401cb9bdc5d0d3f564a3
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